title: Human aquaporins: regulators of transcellular water flow.
abstract: BACKGROUND
  Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistent with their expression in most tissues, AQPs are associated with diverse physiological and pathophysiological processes.
  
  
  METHODS
  AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volume regulation (CVR) is particularly notable. This review examines the regulatory role of AQPs in transcellular water flow, especially in CVR. We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema.
  
  
  CONCLUSIONS
  AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapid movement of water across diverse cell membranes and playing regulatory roles in CVR. Gating mechanisms have been proposed for human AQPs, but have only been reported for plant and microbial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow.
  
  
  CONCLUSIONS
  Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Day
authors.affiliation: Molecular Organisation and Assembly in Cells Doctoral Training Centre, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Kitchen
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Owen
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bland
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Marshall
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: a.c.conner@bham.ac.uk.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Conner
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: r.m.bill@aston.ac.uk.
authors.forename: Roslyn M
authors.initials: RM
authors.lastname: Bill
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK. Electronic address: M.Conner@shu.ac.uk.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Conner
mesh_terms: D020346:Aquaporins / Q000502:physiology*; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism*; D048429:Cell Size; D006801:Humans
chemical_list: D020346:Aquaporins
keywords: Aquaporin regulation; Cell volume regulation; Homeostasis; Regulatory volume decrease; Regulatory volume increase; Transcellular water flow